ObesityPhase 4MODELNCT02911818
Lifestyle Modification and Liraglutide
A Phase 4 study testing CMS-recommended lifestyle counseling, Liraglutide 3.0mg and Phentermine 15 MG in people with Obesity, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is a 52 week, single center, open-labeled, randomized controlled trial. A total of 150 subjects with obesity, who are free of types 1 and 2 diabetes, as well as contraindications to weight loss, will be randomly assigned to one of three treatment groups: 1) lifestyle counseling, as currently recommended by the… Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Obesity
- What is being tested?
- CMS-recommended lifestyle counseling, Liraglutide 3.0mg and Phentermine 15 MG
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to Dec 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have a BMI ≥ 30 and ≤ 55 kg/m²
- Age ≥ 21 years and ≤ 70 years
- Eligible female patients will be:
- non-pregnant, evidenced by a negative urine dipstick pregnancy test
- non-lactating
- surgically sterile or postmenopausal, or they will agree to continue to use an accepted method of birth control during the study
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- Ability to provide informed consent before any trial-related activities
- Participants must:
- have a primary care provider (PCP) who is responsible for providing routine care
- have a reliable telephone service with which to communicate with study staff
- understand and be willing to comply with all study-related procedures and agree to participate in the study by giving written informed consent
- plan to remain in the Philadelphia area for the next 18 months
- Inclusion criteria are those described for the original 1-year trial (enumerated above). The principal exception from these criteria is that participants will only be required to have a BMI > 27 kg/m2, with or without co-morbidities, to be eligible to participate in the extension study. All participants will have met BMI inclusion criteria when they initiated the use of liraglutide and now will use it, potentially with phentermine 15 mg/d, to facilitate to the maintenance of lost weight. (Liraglutide is approved for chronic weight management, including following successful weight loss.) We do not wish to enroll participants with a BMI < 27 kg/m2 because of the possibility that they could reduce substantially below a BMI of 24.9 kg/m2, the upper limit of "normal" weight.
Who cannot join
- Pregnant or nursing, or plans to become pregnant in the next 18 months, or not using adequate contraceptive measures
- Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2
- Uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mm Hg)
- Type 1 diabetes
- Type 2 diabetes
- A fasting glucose ≥ 126 mg/dl (on second assessment after first elevated value)
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- Recent history of cardiovascular disease (e.g., myocardial infarction or stroke within the past 6 months), congestive heart failure, or heart block greater than first degree
- Clinically significant hepatic or renal disease
- Thyroid disease, not controlled
- History of malignancy (except for non-melanoma skin cancer) in past 5 years
- Current major depressive episode, active suicidal ideation, or history of suicide attempts
- Psychiatric hospitalization within the past 6 months
- Self-reported alcohol or substance abuse within the past 12 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)
- Use in past 3 months of medications known to induce significant weight loss (i.e., prescription weight loss medications) or weight gain (e.g., chronic use of oral steroids, second generation antipsychotics)
- Loss of ≥ 10 lb of body weight within the past 3 months
- History of (or plans for) bariatric surgery
- Inability to walk 5 blocks comfortably or engage in some other form of aerobic activity (e.g., swimming)
- Known or suspected allergy to trial medication(s), excipients, or related products
- Hypersensitivity to liraglutide or any product components
- The receipt of any investigational drug within 6 months prior to this trial
- Previous participation in this trial (e.g., randomized and failed to participate)
- History of pancreatitis
- Subjects will be included/excluded according to the latest updated US PI.
- 12-Week Extension Trial:
- Exclusion criteria will include those listed in the original protocol, including those specific to the use of liraglutide 3.0 mg/d (e.g., family history of medullary thyroid cancer).
- Additional exclusion criteria added to the 12-week extension study are specific to the use of phentermine 15 mg/d. They include:
- Use of monoamine oxidase inhibitors in the past 2 weeks
- Glaucoma
- Presence or history of marked agitation
- History of drug abuse
- Known hypersensitivity to sympathomimetic amines
- Current use of selective serotonin re-uptake inhibitors (e.g., fluoxetine, sertraline, etc)
- Current use of any other weight loss medications (besides liraglutide 3.0 mg/d)
- History of coronary artery disease
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania Center for Weight and Eating Disorders
Philadelphia, Pennsylvania, 19104
About this study
Official title: Combining Lifestyle Modification and Liraglutide to Improve Weight Loss and Health Outcomes
This is a 52 week, single center, open-labeled, randomized controlled trial.
A total of 150 subjects with obesity, who are free of types 1 and 2 diabetes, as well as contraindications to weight loss, will be randomly assigned to one of three treatment groups: 1) lifestyle counseling, as currently recommended by the Centers for Medicare and Medicaid Services (CMS) (i.e., CMS-Alone); 2) CMS lifestyle counseling plus liraglutide (i.e., CMS-Liraglutide); or 3) CMS-Liraglutide plus a portion-controlled diet (i.e., Multi-Component Intervention).
Read more
Subjects in all three groups will have 14 brief (15 minute) lifestyle counseling visits the first 24 weeks, followed by monthly visits in weeks 25-52. This is the schedule and duration of counseling visits recommended by CMS. Counseling sessions will be delivered by a physician, nurse practitioner or registered dietitian (RD) working in consultation with the former providers.
Subjects in all three groups also will have brief physician visits at weeks 1, 4, 8, 16, 24, 36, and 52 (total of 7 visits). These visits are needed for subjects in both liraglutide groups to monitor their response to the medication. These visits are included for subjects in CMS-Alone to match the intensity of medical care provided the two other groups.
The primary outcome is % reduction in initial body weight, as measured from randomization to week 52. Secondary outcomes include the proportion of participants who at week 52 lose >5%, >10%, and >15% of initial weight, as well as % reduction in weight at week 24 and the proportion of participants who meet the three categorical weight losses at this time. The secondary efficacy measures include changes (from randomization to week 52) in cardiovascular disease (CVD) risk factors, glycemic control, mood, quality of life, eating behavior, appetite, sleep, and satisfaction with weight loss.
Safety endpoints will include physical examination, adverse events (AEs), standard laboratory tests, and mental health assessed by the Columbia Suicidality Severity Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9).
Statistical Analysis. Using a sample size equation for longitudinal clustered samples, a randomization sample of 50 subjects in CMS-Alone, 50 in CMS-Liraglutide, and 50 in the Multi-Component Intervention provides >80% power to detect the two primary contrasts to be statistically significant. This estimate allows for 20% attrition during the 52-week trial, resulting in approximately 40 treatment completers per group. The ITT longitudinal statistical design will further improve power by allowing the inclusion of available data for non-completers and the adjustment of possible variance reducing baseline covariates.
Read the detailed description
The addendum to the original 52-week trial, is a 12-week, single center, randomized placebo-controlled, parallel group designed trial. This 12-week extension study is separate from the original 52-week trial and will not affect the outcome or analysis of the 52-week, 3-arm trial.
Participants and investigators will be masked to participants' assignment to phentermine 15 mg/d versus placebo. Participants in both groups will receive liraglutide in an open-label manner.
We anticipate that 23 (of 50) participants from the original CMS-Liraglutide group and 23 (of 50) from the Multi-Component Intervention will be eligible to participate in the extension study and will elect to do so. We anticipate that 20 participants in each group will complete the 12-week extension study and that those who receive liraglutide 3.0 mg plus phentermine 15.0 mg/d will lose, from randomization to week 12, 3.5+3.5% of initial weight, compared with 0.0+0.5% for those assigned to liraglutide plus placebo.
All participants in the extension study will meet with a physician or nurse practitioner at randomization (week 0) and at weeks 2, 4, 8 and 12. On each occasion they will review patients' blood pressure and pulse, assess suicidal ideation, and record and respond appropriately to reports of changes in physical health. As during the 1-year prior trial, brief lifestyle counseling (15 min) will provided at monthly visits (excluding week 2) by the physician or nurse practitioner or by a registered dietitian or behavioral psychologist, working under their supervision. The lifestyle intervention will be the same as that provided during the last 6 months of both the CMS-Liraglutide and Multi-Component interventions.
Following the 12-week randomized trial, phentermine (or placebo) will be terminated, and all participants will continue to receive liraglutide 3.0 mg/d for an additional 8 weeks (i.e., weeks 12-20) and have lifestyle counseling and medical assessments at weeks 16 and 20. Liraglutide 3.0 mg/d will be terminated at week 20, and participants will have a final safety assessment at week 24.
The primary endpoint of the 12-week extension trial is change in body weight (i.e., % reduction in randomization weight), as measured from randomization (week 0) to week 12. Secondary endpoints include the proportion of subjects who lose > 5% or > 10% of initial weight from randomization to week 12, as well as changes from randomization to week 12 in cardiovascular disease (CVD) risk factors (i.e, blood pressure, triglycerides, LDL and HDL cholesterol, and waist circumference), glycemic control (i.e., fasting blood sugar), mood (PHQ-9), quality of life (i.e, SF-36 and IWQOL-Lite), eating behavior (i.e., Eating Inventory, Eating Disorder Examination-Questionnaire, and Yale Food Addiction Scale), appetite (i.e., visual analogue scales), sleep (i.e., Pittsburgh Sleep Quality Index), and weight loss satisfaction. (All of these measures were administered in the original 1-year trial.)
Safety endpoints will include physical examination, adverse events (AEs), standard laboratory tests, and mental health assessed by the Columbia Suicidality Severity Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9).
All data analyses will proceed using the same principles and methods used in the original protocol.
- Conditions
- Obesity
- Being tested
- CMS-recommended lifestyle counseling, Liraglutide 3.0mg, Portion-Controlled Diet, Placebo Oral Tablet, Phentermine 15 MG
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMS-recommended lifestyle counselingBehavioural
21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.
Liraglutide 3.0mgDrug
Also called Saxenda
Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection.
Portion-Controlled DietOther
A 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks.
Placebo Oral TabletDrug
Phentermine 15 MGDrug
Extension Study CMS-recommended lifestyle counselingBehavioural
4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.
| Study group | Role | What they receive |
|---|---|---|
| CMS-Alone | Active comparator | Lifestyle counseling, as currently recommended by the CMS. Receives: Behavioral: CMS-recommended lifestyle counseling |
| CMS-Liraglutide | Active comparator | CMS lifestyle counselling plus liraglutide. Receives: Behavioral: CMS-recommended lifestyle counseling; Drug: Liraglutide 3.0mg |
| Multi-Component Intervention | Active comparator | CMS-Liraglutide plus a 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks. Receives: Behavioral: CMS-recommended lifestyle counseling; Drug: Liraglutide 3.0mg; Other: Portion-Controlled Diet |
| 12-Week Extension Study: Phentermine Group | Active comparator | After the 1-year trial, half the participants who join the extension study will be randomized to phentermine 15.0 mg/d in a double-blind fashion, while continuing to take liraglutide. They will also continue to receive monthly lifestyle counseling. To be eligible for the extension study, participants must have been assigned to one of two medication groups in the original study. Receives: Drug: Liraglutide 3.0mg; Drug: Phentermine 15 MG; Behavioral: Extension Study CMS-recommended lifestyle counseling |
| 12-Week Extension Study: Placebo Group | Active comparator | After the 1-year trial, half the participants who join the extension study will be randomized to placebo in a double-blind fashion, while continuing to take liraglutide. They will also continue to receive monthly lifestyle counseling. To be eligible for the extension study, participants must have been assigned to one of two medication groups in the original study. Receives: Drug: Liraglutide 3.0mg; Drug: Placebo Oral Tablet; Behavioral: Extension Study CMS-recommended lifestyle counseling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Baseline Weight
Measured: Randomization and 52 weeks
Extension Study Primary Outcome: Percent Change in Re-randomization Weight
Measured: Re-randomization and 12 weeks
Secondary outcomes (32)
Change in Systolic Blood Pressure
Measured: Randomization and 52 weeks
Change in Diastolic Blood Pressure
Measured: Randomization and 52 weeks
Change in Heart Rate
Measured: Randomization and 52 weeks
Change in Waist Circumference
Measured: Randomization and 52 weeks
Change in Total Cholesterol
Measured: Randomization and 52 weeks
Change in LDL Cholesterol
Measured: Randomization and 52 weeks
Change in HDL Cholesterol
Measured: Randomization and 52 weeks
Change in Triglycerides
Measured: Randomization and 52 weeks
Change in C Reactive Protein
Measured: Randomization and 52 weeks
Change in Fasting Glucose
Measured: Randomization and 52 weeks
Change in HbA1c
Measured: Randomization and 52 weeks
Change in Fasting Insulin
Measured: Randomization and 52 weeks
Change in HOMA-IR
HOMA-IR is a measurement for insulin resistance and is calculated from: fasting insulin (U/L) x fasting glucose (mg/dL)/405. A decrease from baseline to the end of treatment, a negative value, indicates an improvement
Measured: Randomization and 52 weeks
Change in 36-Item Short Form Survey (SF-36) - Physical Component Summary
All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health.
Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10.
Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.
Measured: Randomization and 52 weeks
Change 36-Item Short Form Survey (SF-36) - Mental Component Summary
All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health.
Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10.
Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.
Measured: Randomization and 52 weeks
Change in Patient Health Questionnaire (PHQ-9)
PHQ-9 is scored based on a 0-27 scale in which higher scores indicate more severe depression. Values are summed to compute the total score.
Measured: Randomization and 52 weeks
Extension Study Secondary Outcome: Change in Systolic Blood Pressure
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Diastolic Blood Pressure
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Heart Rate
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Waist Circumference
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Total Cholesterol
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in LDL Cholesterol
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in HDL Cholesterol
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Triglycerides
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in c-Reactive Protein
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Fasting Glucose
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in HbA1c
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Fasting Insulin
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in HOMA-IR
HOMA-IR is a measurement for insulin resistance and is calculated from: fasting insulin (U/L) x fasting glucose (mg/dL)/405. A decrease from baseline to the end of treatment, a negative value, indicates an improvement
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: SF-36 - Physical Health Component
All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health.
Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10.
Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: SF-36 - Mental Health Component
All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health.
Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10.
Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.
Measured: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Patient Health Questionnaire (PHQ-9)
PHQ-9 is scored based on a 0-27 scale in which higher scores indicate more severe depression. Values are summed to compute the total score.
Measured: Re-randomization and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2016 (estimated)
- Study startSep 2016
- Primary completionNov 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
- Investigators
- Thomas A Wadden, Ph.D., Principal investigator, University of Pennsylvania, Center for Weight and Eating Disorders
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02911818
- Sponsor's protocol ID
- 824806
- Acronym
- MODEL
- Status last verified
- Apr 2019
- First submitted
- 6 Sep 2016
- Last updated
- 7 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- No
Publications
Tronieri JS, Wadden TA, Walsh O, Berkowitz RI, Alamuddin N, Gruber K, Leonard S, Bakizada ZM, Chao AM. Effects of liraglutide on appetite, food preoccupation, and food liking: results of a randomized controlled trial. Int J Obes (Lond). 2020 Feb;44(2):353-361. doi: 10.1038/s41366-019-0348-6. Epub 2019 Mar 29.
PubMed 30926955Tronieri JS, Wadden TA, Walsh OA, Berkowitz RI, Alamuddin N, Gruber K, Leonard S, Chao AM. Effects of liraglutide plus phentermine in adults with obesity following 1 year of treatment by liraglutide alone: A randomized placebo-controlled pilot trial. Metabolism. 2019 Jul;96:83-91. doi: 10.1016/j.metabol.2019.03.005. Epub 2019 Mar 20.
PubMed 30902750Wadden TA, Walsh OA, Berkowitz RI, Chao AM, Alamuddin N, Gruber K, Leonard S, Mugler K, Bakizada Z, Tronieri JS. Intensive Behavioral Therapy for Obesity Combined with Liraglutide 3.0 mg: A Randomized Controlled Trial. Obesity (Silver Spring). 2019 Jan;27(1):75-86. doi: 10.1002/oby.22359. Epub 2018 Nov 13.
PubMed 30421856
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining Lifestyle Modification and Liraglutide to Improve Weight Loss and Health Outcomes
- ClinicalTrials.gov ID
- NCT02911818
- Acronym / sponsor ID
- MODEL / 824806
- Conditions
- Obesity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Novo Nordisk A/S
- Study start
- Sep 2016 (actual)
- Primary completion
- Nov 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 22 Sep 2016 (estimated)
- Results
- Posted 7 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 52 week, single center, open-labeled, randomized controlled trial.
A total of 150 subjects with obesity, who are free of types 1 and 2 diabetes, as well as contraindications to weight loss, will be randomly assigned to one of three treatment groups: 1) lifestyle counseling, as currently recommended by the Centers for Medicare and Medicaid Services (CMS) (i.e., CMS-Alone); 2) CMS lifestyle counseling plus liraglutide (i.e., CMS-Liraglutide); or 3) CMS-Liraglutide plus a portion-controlled diet (i.e., Multi-Component Intervention).
Subjects in all three groups will have 14 brief (15 minute) lifestyle counseling visits the first 24 weeks, followed by monthly visits in weeks 25-52. This is the schedule and duration of counseling visits recommended by CMS. Counseling sessions will be delivered by a physician, nurse practitioner or registered dietitian (RD) working in consultation with the former providers.
Subjects in all three groups also will have brief physician visits at weeks 1, 4, 8, 16, 24, 36, and 52 (total of 7 visits). These visits are needed for subjects in both liraglutide groups to monitor their response to the medication. These visits are included for subjects in CMS-Alone to match the intensity of medical care provided the two other groups.
The primary outcome is % reduction in initial body weight, as measured from randomization to week 52. Secondary outcomes include the proportion of participants who at week 52 lose >5%, >10%, and >15% of initial weight, as well as % reduction in weight at week 24 and the proportion of participants who meet the three categorical weight losses at this time. The secondary efficacy measures include changes (from randomization to week 52) in cardiovascular disease (CVD) risk factors, glycemic control, mood, quality of life, eating behavior, appetite, sleep, and satisfaction with weight loss.
Safety endpoints will include physical examination, adverse events (AEs), standard laboratory tests, and mental health assessed by the Columbia Suicidality Severity Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9).
Statistical Analysis. Using a sample size equation for longitudinal clustered samples, a randomization sample of 50 subjects in CMS-Alone, 50 in CMS-Liraglutide, and 50 in the Multi-Component Intervention provides >80% power to detect the two primary contrasts to be statistically significant. This estimate allows for 20% attrition during the 52-week trial, resulting in approximately 40 treatment completers per group. The ITT longitudinal statistical design will further improve power by allowing the inclusion of available data for non-completers and the adjustment of possible variance reducing baseline covariates.
Detailed description
The addendum to the original 52-week trial, is a 12-week, single center, randomized placebo-controlled, parallel group designed trial. This 12-week extension study is separate from the original 52-week trial and will not affect the outcome or analysis of the 52-week, 3-arm trial.
Participants and investigators will be masked to participants' assignment to phentermine 15 mg/d versus placebo. Participants in both groups will receive liraglutide in an open-label manner.
We anticipate that 23 (of 50) participants from the original CMS-Liraglutide group and 23 (of 50) from the Multi-Component Intervention will be eligible to participate in the extension study and will elect to do so. We anticipate that 20 participants in each group will complete the 12-week extension study and that those who receive liraglutide 3.0 mg plus phentermine 15.0 mg/d will lose, from randomization to week 12, 3.5+3.5% of initial weight, compared with 0.0+0.5% for those assigned to liraglutide plus placebo.
All participants in the extension study will meet with a physician or nurse practitioner at randomization (week 0) and at weeks 2, 4, 8 and 12. On each occasion they will review patients' blood pressure and pulse, assess suicidal ideation, and record and respond appropriately to reports of changes in physical health. As during the 1-year prior trial, brief lifestyle counseling (15 min) will provided at monthly visits (excluding week 2) by the physician or nurse practitioner or by a registered dietitian or behavioral psychologist, working under their supervision. The lifestyle intervention will be the same as that provided during the last 6 months of both the CMS-Liraglutide and Multi-Component interventions.
Following the 12-week randomized trial, phentermine (or placebo) will be terminated, and all participants will continue to receive liraglutide 3.0 mg/d for an additional 8 weeks (i.e., weeks 12-20) and have lifestyle counseling and medical assessments at weeks 16 and 20. Liraglutide 3.0 mg/d will be terminated at week 20, and participants will have a final safety assessment at week 24.
The primary endpoint of the 12-week extension trial is change in body weight (i.e., % reduction in randomization weight), as measured from randomization (week 0) to week 12. Secondary endpoints include the proportion of subjects who lose > 5% or > 10% of initial weight from randomization to week 12, as well as changes from randomization to week 12 in cardiovascular disease (CVD) risk factors (i.e, blood pressure, triglycerides, LDL and HDL cholesterol, and waist circumference), glycemic control (i.e., fasting blood sugar), mood (PHQ-9), quality of life (i.e, SF-36 and IWQOL-Lite), eating behavior (i.e., Eating Inventory, Eating Disorder Examination-Questionnaire, and Yale Food Addiction Scale), appetite (i.e., visual analogue scales), sleep (i.e., Pittsburgh Sleep Quality Index), and weight loss satisfaction. (All of these measures were administered in the original 1-year trial.)
Safety endpoints will include physical examination, adverse events (AEs), standard laboratory tests, and mental health assessed by the Columbia Suicidality Severity Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9).
All data analyses will proceed using the same principles and methods used in the original protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| CMS-Alone | Active comparator | Behavioral: CMS-recommended lifestyle counselingLifestyle counseling, as currently recommended by the CMS. |
| CMS-Liraglutide | Active comparator | Behavioral: CMS-recommended lifestyle counseling, Drug: Liraglutide 3.0mgCMS lifestyle counselling plus liraglutide. |
| Multi-Component Intervention | Active comparator | Behavioral: CMS-recommended lifestyle counseling, Drug: Liraglutide 3.0mg, Other: Portion-Controlled DietCMS-Liraglutide plus a 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks. |
| 12-Week Extension Study: Phentermine Group | Active comparator | Drug: Liraglutide 3.0mg, Drug: Phentermine 15 MG, Behavioral: Extension Study CMS-recommended lifestyle counselingAfter the 1-year trial, half the participants who join the extension study will be randomized to phentermine 15.0 mg/d in a double-blind fashion, while continuing to take liraglutide. They will also continue to receive monthly lifestyle counseling. To be eligible for the extension study, participants must have been assigned to one of two medication groups in the original study. |
| 12-Week Extension Study: Placebo Group | Active comparator | Drug: Liraglutide 3.0mg, Drug: Placebo Oral Tablet, Behavioral: Extension Study CMS-recommended lifestyle counselingAfter the 1-year trial, half the participants who join the extension study will be randomized to placebo in a double-blind fashion, while continuing to take liraglutide. They will also continue to receive monthly lifestyle counseling. To be eligible for the extension study, participants must have been assigned to one of two medication groups in the original study. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Participants must have a BMI ≥ 30 and ≤ 55 kg/m²
- Age ≥ 21 years and ≤ 70 years
- Eligible female patients will be:
- Ability to provide informed consent before any trial-related activities
- Participants must:
Key exclusion criteria (34 listed)
- Pregnant or nursing, or plans to become pregnant in the next 18 months, or not using adequate contraceptive measures
- Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2
- Uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mm Hg)
- Type 1 diabetes
- Type 2 diabetes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CMS-recommended lifestyle counseling21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. | Behavioural | CMS-Alone, CMS-Liraglutide, Multi-Component Intervention |
| Liraglutide 3.0mgAlso: SaxendaLiraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. | Drug | 12-Week Extension Study: Phentermine Group, 12-Week Extension Study: Placebo Group, CMS-Liraglutide, Multi-Component Intervention |
| Portion-Controlled DietA 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks. | Other | Multi-Component Intervention |
| Placebo Oral Tablet | Drug | 12-Week Extension Study: Placebo Group |
| Phentermine 15 MG | Drug | 12-Week Extension Study: Phentermine Group |
| Extension Study CMS-recommended lifestyle counseling4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. | Behavioural | 12-Week Extension Study: Phentermine Group, 12-Week Extension Study: Placebo Group |
Primary outcome
Percent Change in Baseline Weight
Time frame: Randomization and 52 weeks
Extension Study Primary Outcome: Percent Change in Re-randomization Weight
Time frame: Re-randomization and 12 weeks
32 secondary outcomes
Change in Systolic Blood Pressure
Time frame: Randomization and 52 weeks
Change in Diastolic Blood Pressure
Time frame: Randomization and 52 weeks
Change in Heart Rate
Time frame: Randomization and 52 weeks
Change in Waist Circumference
Time frame: Randomization and 52 weeks
Change in Total Cholesterol
Time frame: Randomization and 52 weeks
Change in LDL Cholesterol
Time frame: Randomization and 52 weeks
Change in HDL Cholesterol
Time frame: Randomization and 52 weeks
Change in Triglycerides
Time frame: Randomization and 52 weeks
Change in C Reactive Protein
Time frame: Randomization and 52 weeks
Change in Fasting Glucose
Time frame: Randomization and 52 weeks
Change in HbA1c
Time frame: Randomization and 52 weeks
Change in Fasting Insulin
Time frame: Randomization and 52 weeks
Change in HOMA-IR
Time frame: Randomization and 52 weeks
Change in 36-Item Short Form Survey (SF-36) - Physical Component Summary
Time frame: Randomization and 52 weeks
Change 36-Item Short Form Survey (SF-36) - Mental Component Summary
Time frame: Randomization and 52 weeks
Change in Patient Health Questionnaire (PHQ-9)
Time frame: Randomization and 52 weeks
Extension Study Secondary Outcome: Change in Systolic Blood Pressure
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Diastolic Blood Pressure
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Heart Rate
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Waist Circumference
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Total Cholesterol
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in LDL Cholesterol
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in HDL Cholesterol
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Triglycerides
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in c-Reactive Protein
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Fasting Glucose
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in HbA1c
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in Fasting Insulin
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Change in HOMA-IR
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: SF-36 - Physical Health Component
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: SF-36 - Mental Health Component
Time frame: Re-randomization and 12 weeks
Extension Study Secondary Outcome: Patient Health Questionnaire (PHQ-9)
Time frame: Re-randomization and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30926955Tronieri JS, Wadden TA, Walsh O, Berkowitz RI, Alamuddin N, Gruber K, Leonard S, Bakizada ZM, Chao AM. Effects of liraglutide on appetite, food preoccupation, and food liking: results of a randomized controlled trial. Int J Obes (Lond). 2020 Feb;44(2):353-361. doi: 10.1038/s41366-019-0348-6. Epub 2019 Mar 29.
- Derived from this study: PubMed 30902750Tronieri JS, Wadden TA, Walsh OA, Berkowitz RI, Alamuddin N, Gruber K, Leonard S, Chao AM. Effects of liraglutide plus phentermine in adults with obesity following 1 year of treatment by liraglutide alone: A randomized placebo-controlled pilot trial. Metabolism. 2019 Jul;96:83-91. doi: 10.1016/j.metabol.2019.03.005. Epub 2019 Mar 20.
- Derived from this study: PubMed 30421856Wadden TA, Walsh OA, Berkowitz RI, Chao AM, Alamuddin N, Gruber K, Leonard S, Mugler K, Bakizada Z, Tronieri JS. Intensive Behavioral Therapy for Obesity Combined with Liraglutide 3.0 mg: A Randomized Controlled Trial. Obesity (Silver Spring). 2019 Jan;27(1):75-86. doi: 10.1002/oby.22359. Epub 2018 Nov 13.
- Center for Weight and Eating Disorders WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas A Wadden, Ph.D. principal investigator
University of Pennsylvania, Center for Weight and Eating Disorders
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing CMS-recommended lifestyle counseling, Liraglutide 3.0mg and Phentermine 15 MG in people with Obesity, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Baseline Weight (time frame: Randomization and 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02911818, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2019; AzTrials last refreshed its copy on 1 Nov 2026.